Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi
InTrypanosoma cruzithe isoprenoid and sterol biosynthesis pathways are validated targets for chemotherapeuticintervention. In this work we present a study of the genetic diversity observed in genes from these pathways. Using anumber of bioinformatic strategies, we first identified genes that were mi...
| Autores: | , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/32326 |
| Acceso en línea: | http://hdl.handle.net/11336/32326 |
| Access Level: | acceso abierto |
| Palabra clave: | trypanosoma cruzi sterol biosynthesis pathway isoprenoid biosynthesis pathway SNPs https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| Sumario: | InTrypanosoma cruzithe isoprenoid and sterol biosynthesis pathways are validated targets for chemotherapeuticintervention. In this work we present a study of the genetic diversity observed in genes from these pathways. Using anumber of bioinformatic strategies, we first identified genes that were missing and/or were truncated in theT. cruzigenome. Based on this analysis we obtained the complete sequence of the ortholog of the yeast ERG26 gene and identifieda non-orthologous homolog of the yeast ERG25 gene (sterol methyl oxidase, SMO), and we propose that the orthologs ofERG25 have been lost in trypanosomes (but not in Leishmanias). Next, starting from a set of 16T. cruzistrains representativeof all extant evolutionary lineages, we amplified and sequenced,24 Kbp from 22 genes, identifying a total of 975 SNPs orfixed differences, of which 28% represent non-synonymous changes. We observed genes with a density of substitutionsranging from those close to the average (,2.5/100 bp) to some showing a high number of changes (11.4/100 bp, for theputative lathosterol oxidase gene). All the genes of the pathway are under apparent purifying selection, but genes codingfor the sterol C14-demethylase, the HMG-CoA synthase, and the HMG-CoA reductase have the lowest density of missenseSNPs in the panel. Other genes (TcPMK, TcSMO-like) have a relatively high density of non-synonymous SNPs (2.5 and 1.9every 100 bp, respectively). However, none of the non-synonymous changes identified affect a catalytic or ligand bindingsite residue. A comparative analysis of the corresponding genes from African trypanosomes andLeishmaniashows similarlevels of apparent selection for each gene. This information will be essential for future drug development studies focused onthis pathway. |
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